We will expand our ongoing studies of the interactions of neutrophil elastase, serum trypsin inhibitory activity (TIA) and smoking history (pack years) as risk factors for pulmonary function derangements of chronic obstructive lung disease (COPD) in patients with M, MZ, and Z (Pi) phenotypes for alpha1 -antitrypsin (AAT). We will search for additional neutrophil protease-serum antiprotease relationships and include in our analysis aspects of smoking history not previously considered. The role of PMN elastase content and of smoking history in the rate of secretion of elastase by neutrophils of patients with COPD and of healthy controls will be studied. In addition, we will investigate whether some individuals despite having normal serum trypsin inhibitory activity are prone to develop COPD because their serum has a limited capacity to inhibit elastase released by their own neutrophils. We will also investigate whether elastin becomes a better substrate for PMN elastase when it is complexed with anionic amphilhilic agents to which it may be exposed in vivo.